Sertraline

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Sertraline

Examples of brand names: Zoloft [DE]

ATC code: N06AB06

Main use (for orientation): Depression; anxiety

Documented research summary

The previously recorded CBD–sertraline hyponatraemia case was rechecked against the full text: CYP2C19*1/*2, additional medication including omeprazole, no measured increase in sertraline concentration. Additional retrospective cases involving cannabis flowers or 10% CBD oil show warning signals, but no causally confirmed enzyme mechanisms. A pharmacokinetic model explicitly assumes a 25% reduction in clearance rather than measuring it. Two mouse models produced different behavioural findings for the CBD–sertraline combination; no treatment recommendation for humans. An in-vitro metabolism study reported only minor CBD effects on sertraline.

Uncertainties and limitations

Nanan case without a CBD dose, product analysis or sertraline pharmacokinetics; omeprazole and genotype are possible additional influences.

The Vaughn model is based on an assumed 25% reduction in clearance. Low CBD quantities or THC are not presented as clinically proven causes of the modelled AUC increase.

The Chrobak case series is selected, involves polypharmacy and has no pharmacokinetic measurements. The proposed CYP mechanisms are hypotheses.

Do not derive current pharmacogenetic dosage recommendations from guideline statements in older case reports.

Historical secondary-source lead in Chapin 2025: sertraline / desipramine / cannabis, DIPS=0; unclear whether the antidepressants were used simultaneously or sequentially, and the reference number is inconsistent. Without the original clinical course, it was not accepted as an established sertraline pair interaction.

Separately recorded findings

8 separately recorded findings. Each statement applies to its documented study context.

CBD – clinical signals

Finding ID: B0101

Type of result: Context-specific finding; read the limitations

Observation: Hyponatraemia and cognitive symptoms reported after adding CBD.

Mechanism: Possible CYP2C19 phenoconversion; genotype *1/*2

Study type: Case report with pharmacogenetics

Context studied: Single case; additional medication included omeprazole.

Clinical interpretation: Individual medical / pharmaceutical assessment; do not use as dosage instructions

Limitations and uncertainties: No directly measured increase in sertraline concentration established. Causality and product composition are uncertain.

Original sources for this finding: Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient [EX13]

CBD – laboratory and animal studies

Finding ID: B0413

Type of result: Substrate / isoenzyme-specific in-vitro inhibition and null findings

Observation: In a recombinant enzyme experiment, CBD inhibited CYP2C9-mediated sertraline metabolism (Ki 1.1 µM), with weaker inhibition of CYP2C19 (Ki 5.9 µM); CYP3A4-mediated sertraline metabolism was not inhibited. This is not a clinical null finding for sertraline.

Mechanism: Investigation of CBD-related inhibition of metabolism

Study type: In-vitro metabolism study

Context studied: The original study also includes a human arm involving citalopram/escitalopram, not this active substance.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: The authors' full-text version (tables and text presented in HTML) was reviewed. The human arm of this study concerns only the mixed citalopram/escitalopram series. No clinical safety or efficacy conclusion for this active substance; time-dependent inhibition and other mechanisms were not comprehensively investigated.

Original sources for this finding: Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People [CL10]

10% CBD oil – clinical signals

Finding ID: B0418

Type of result: Clinical warning signals, mechanism unconfirmed

Observation: Vomiting, diarrhoea and fever were reported in one woman, and severe tiredness in another.

Mechanism: CYP inhibition as a hypothesis; no concentration measurements

Study type: Two cases from a retrospective adverse-effect analysis

Context studied: Sertraline 100 mg/day in each case; 10% CBD oil, amount of CBD consumed in mg not reported; additional medicines including analgesics.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: Selected, confounded cases; no quantified risk. According to its product information, sertraline is not a clinically important strong CYP3A4 inhibitor; the contrary blanket explanation in the case table was not adopted.

Original sources for this finding: Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs. [CA_P_39502532]

THC-rich cannabis flowers; CBD ≤1% – clinical signals

Finding ID: B0419

Type of result: Confounded clinical warning signals

Observation: Cases include ataxia / marked impairment of consciousness, hallucinations / anxiety / tachycardia, ventricular tachycardia, and vomiting or dizziness.

Mechanism: Possible pharmacokinetic / CNS / cardiovascular interaction; not established

Study type: Five cases from a retrospective adverse-effect analysis

Context studied: Cannabis flowers containing 18–22% THC and very little CBD; different sertraline quantities and concomitant medicines.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: Not five independent controlled studies. No isolated THC assessment, no measured change in exposure and no incidence estimate. The events in the affected people are serious; causality for the pair remains uncertain.

Original sources for this finding: Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs. [CA_P_39502532]

CBD or THC; simplified model assumption – theoretical plausibility

Finding ID: B0420

Type of result: Model prediction, not measured human pharmacokinetics

Observation: For sertraline 150 mg/day, the model predicted AUC +33%, Cmax +26% and an increase in half-life from 22.1 to 29.5 hours.

Mechanism: Assumed 25% reduction in clearance

Study type: Pharmacokinetic simulation in modelled adolescents

Context studied: The reduction in clearance is an input assumption, not a measured change with the combination.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: No clinically established dose threshold for CBD/THC. The FAERS analysis in the same paper combines several SSRIs; its reporting ratios are not attributed to sertraline alone.

Original sources for this finding: The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations. [CA_P_34209709]

CBD – laboratory and animal studies

Finding ID: B0421

Type of result: Preclinical, endpoint-dependent combination effect

Observation: The combination was similar to CBD alone in several tests; for sucrose intake, CBD alone was better than the combination. The authors report additional differences in cognition and neuroplasticity markers.

Mechanism: Model-dependent behavioural and gene-expression changes

Study type: Chronic stress model in male CD1 mice

Context studied: After four weeks of stress: 28 days of CBD 20 mg/kg intraperitoneally twice daily and sertraline 10 mg/kg orally once daily; n=12 per stressed treatment arm.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: Not a human study, and no drug pharmacokinetics measured. No recommendation to replace sertraline or use CBD. The abstract describes a less favourable NOR effect of the combination; the results section does not clearly quantify the direct difference between CBD and the combination. Therefore, no definite direction or magnitude is reported for this NOR pair comparison.

Original sources for this finding: Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model. [RMED37144214]

CBD – laboratory and animal studies

Finding ID: B0422

Type of result: Preclinical finding with an internal reporting inconsistency

Observation: The combination showed numerically greater behavioural changes. In the results section, its advantage over the individual treatments did not reach statistical significance for freezing / the light–dark test / the plus maze; an interaction in Crf gene expression was significant.

Mechanism: Behavioural and gene-expression endpoints

Study type: Chronic PTSD model in male C57BL/6J mice

Context studied: CBD 20 mg/kg intraperitoneally and sertraline 10 mg/kg orally once daily in weeks 11–14; approximately 9–10 animals per group.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: The abstract and parts of the figure legends make stronger statements than the statistical results section. Therefore, no established behavioural synergy is claimed. No evidence of efficacy or safety in humans.

Original sources for this finding: Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD. [RMED34262461]

Cannabis; composition not quantified – insufficient data

Finding ID: B0424

Type of result: Multiple-substance context, no isolatable drug–drug interaction

Observation: Confusion, hallucinations and sinus tachycardia after cannabis and a powder containing several prescription medicines.

Mechanism: Combined exposure; the mechanism of an individual pair cannot be determined

Study type: Multiple-substance intoxication case

Context studied: 16-year-old female patient; analysis identified several antidepressants and trihexyphenidyl in the powder.

Clinical interpretation: Interpret within the stated study context; no independent dosage or treatment recommendation.

Limitations and uncertainties: No isolated pair finding; individual quantities unknown and extensive exposure to multiple substances. Listed as safety context, not as an established cannabinoid interaction.

Original sources for this finding: Psychoactive cocktail consumption on Reunion Island: a case report. [BMED39953779]

References and access status

[RLABEL_D0092] SERTRALINE HCL (SERTRALINE HYDROCHLORIDE) CAPSULE [ALMATICA PHARMA LLC]

Original source / bibliographic reference

Authors: Regulatory product information; respective marketing authorisation holder

Year: 2026

Source type: Product information / SmPC / US Prescribing Information

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[CA_P_39502532] Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs.

Original source / bibliographic reference

Authors: Chrobak AA, Woroń J, Siwek M.

Year: 2024

Source type: research-article; Journal Article

DOI: 10.3389/fphar.2024.1500312

PMID: 39502532

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[CA_P_34209709] The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.

Original source / bibliographic reference

Authors: Vaughn SE, Strawn JR, Poweleit EA, Sarangdhar M, Ramsey LB.

Year: 2021

Source type: other; Journal Article

DOI: 10.3390/jpm11070615

PMID: 34209709

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[EX13] Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient

Original source / bibliographic reference

Authors: Nanan JC; Crosby S; Schuh MJ

Year: 2022

Source type: Case report with pharmacogenetics

DOI: 10.24926/iip.v13i3.4890

PMID: 36627907

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[RMED37144214] Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model.

Original source / bibliographic reference

Authors: García-Gutiérrez MS, Navarro D, Austrich-Olivares A, Manzanares J.

Year: 2023

Source type: Original publication; see finding for study type

DOI: 10.3389/fphar.2023.1171646

PMID: 37144214

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

[CL10] Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People

Original source / bibliographic reference

Authors: Anderson LL; Doohan PT; Oldfield L; Kevin RC; Arnold JC; Berger M; Amminger GP; McGregor IS

Year: 2021

Source type: In-vitro study plus a small accompanying clinical investigation

DOI: 10.1097/JCP.0000000000001427

PMID: 34121064

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[RMED34262461] Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD.

Original source / bibliographic reference

Authors: Gasparyan A, Navarrete F, Manzanares J.

Year: 2021

Source type: Original publication; see finding for study type

DOI: 10.3389/fphar.2021.694510

PMID: 34262461

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

[BMED39953779] Psychoactive cocktail consumption on Reunion Island: a case report.

Original source / bibliographic reference

Authors: Guyon J, Maillot A, Bastard S, Weisse F, Daveluy A, Mété D.

Year: 2025

Source type: Publication; title and abstract reviewed

DOI: 10.1093/jat/bkaf009

PMID: 39953779

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

DOI – publisher access (access restrictions may apply)

[BMED39719830] Part 1: Evaluation of Pediatric Cannabis-Drug Interaction Reports.

Original source / bibliographic reference

Authors: Chapin MR, Kane-Gill SL, Li X, Abanyie K, Taneja SB, Egbert S, Paine MF, Boyce RD.

Year: 2025

Source type: Secondary case review and FAERS analysis

DOI: 10.1002/prp2.70046

PMID: 39719830

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

PubMed – bibliographic reference / abstract

PubMed Central – archived text

DOI – publisher access (access restrictions may apply)

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility